Long non-coding RNA X-inactive specific transcript (LncRNA XIST) is involved in several diseases. However, the molecular mechanism of XIST and its relation with miR-133a-3p in contrast-induced nephropathy (CIN) remained vague. Sprague-Dawley (SD) rats were assigned to Control, Sham, and CIN groups at random (n = 15 for each group). Histological examination on the kidney tissues was performed using hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) staining. Mean serum creatinine (SCr) and blood urea nitrogen (BUN) contents was measured by colorimetric microplate method. Levels of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The cells viability and apoptosis were respectively detected by MTT assay and flow cytometry. Target gene and potential binding sites between XIST, miR-133a-3p and NLR Family Pyrin Domain Containing 3 (NLRP3) were predicted using online databases and confirmed by dual-luciferase reporter assay. Relative mRNA and protein expressions of XIST, miR-133a-3p, NLRP3, apoptosis-associated speck-like protein (ASC) and Cleaved caspase-1 were measured with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. In the rat CIN model, Ioversol induced kidney morphology changes, with increase on SCr and BUN contents, elevated levels of inflammatory cytokines and upregulated expressions of XIST, NLRP3, ASC and Cleaved caspase-1. Silencing XIST reversed the effects of Ioversol on cells. MiR-133a-3p could bind with XIST and target NLRP3, and downregulating miR-133a-3p reversed the effect of silencing XIST on Ioversol-treated cells. Moreover, downregulating XIST attenuated CIN injury via regulating miR-133a-3p/NLRP3 axis.